Hypertension

Abstract

Blockers of the renin–angiotensin–aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension.

Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury

“…11 A current hypothesis is that such untoward effects are because of excessive renal RAAS inhibition. 12 Thus, a more effective therapeutic strategy would (1) work upstream of the RAAS enzymes and receptors, thereby avoiding compensatory mechanisms and intracrine signaling that limit therapeutic efficacy, and (2) have limited kidney activity, thereby providing the benefits of aggressive RAAS suppression without provoking renal complications.…”

Neuro-Humoral Disbalance in Chronic Heart Failure: Classic and Modern Perspectives

“…д.). При фокусировке на стенке сосуда активация рецепторов АТ 1 вызывает вазоконстрик-цию, эндотелиальную дисфункцию, воспаление, рост и ремоделирование, тогда как АТ 2 -рецепторы, как полагают, противодействуют этим эффектам [9].…”

“…Подобно A-II, альдостерон является эффектор-ным гормоном РААС, главным образом, участвует в регуляции объема и АД [9]. Он может индуцировать воспаление в эндотелии коронарных сосудов и пери-васкулярных зонах миокарда, опосредованно участ-вуя в вазоконстрикции [9].…”

“…Он может индуцировать воспаление в эндотелии коронарных сосудов и пери-васкулярных зонах миокарда, опосредованно участ-вуя в вазоконстрикции [9]. В когортных исследова-ниях негипертензивных индивидуумов более высо-кие уровни циркулирующего альдостерона (даже в пределах физиологического диапазона), являются фактором риска развития гипертензии [10].…”

Angiotensin Type 2 Receptor

“…A caveat to this conclusion is that supporting evidence available in humans is limited. 8,9 Men die at a greater rate of cardiovascular-related diseases, except at the oldest ages, when compared with women. Thus, understanding how the AT 2 R is upregulated in women and repressed in men could be used to lower morbidity and mortality in men at all ages, and maintain protection in postmenopausal women, and this possibility should be explored further.…”